Classifications

• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
  • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
  • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
  • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
  • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
  • G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
  • G01N33/54366—Apparatus specially adapted for solid-phase testing
  • G01N33/54373—Apparatus specially adapted for solid-phase testing involving physiochemical end-point determination, e.g. wave-guides, FETS, gratings
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
  • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
  • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
  • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
  • B01J2219/00277—Apparatus
  • B01J2219/00351—Means for dispensing and evacuation of reagents
  • B01J2219/00436—Maskless processes
  • B01J2219/00439—Maskless processes using micromirror arrays
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
  • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
  • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
  • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
  • B01J2219/0068—Means for controlling the apparatus of the process
  • B01J2219/00695—Synthesis control routines, e.g. using computer programs
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
  • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
  • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
  • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
  • B01J2219/0068—Means for controlling the apparatus of the process
  • B01J2219/00702—Processes involving means for analysing and characterising the products
  • B01J2219/00707—Processes involving means for analysing and characterising the products separated from the reactor apparatus
• • C—CHEMISTRY; METALLURGY
  • C40—COMBINATORIAL TECHNOLOGY
  • C40B—COMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES
  • C40B60/00—Apparatus specially adapted for use in combinatorial chemistry or with libraries
  • C40B60/14—Apparatus specially adapted for use in combinatorial chemistry or with libraries for creating libraries

Definitions

• This invention relates to a method of detecting and screening organic molecules and biologic pathogens by employing molecular probe activated digital micromirror technology.
• a first field of science relevant to the invention is the detection and identification of biologic molecules and pathogens.
• a multiplicity of detection sites are formed on a suitable substrate and a sample substance containing molecular structures sought to be detected and identified is applied over the sites.
• Each test site contains probes designed to bond with a predetermined target molecular structure.
• the probes in each site differ in a predetermined known manner from the probes in the other sites so that different target molecules in the sample may bond with different probes.
• a signal is applied to the test sites and certain electrical, mechanical and/or optical properties of the sites are detected to determine which probes have bonded to an associated target molecular structure.
• the bonded molecules may then be removed from the respective sites and subjected to testing and analysis.
• a second field of technology relevant to the invention is that relating to digital light processing display technology based on a microelectromechanical systems device known as the digital micromirror device.
• a digital micromirror device is comprised of thousands, even hundreds of thousands, of individual mirrors, each usually sixteen microns square, and each fabricated on hinges on top of a static random access memory (SRAM). Each mirror is capable of receiving its own unique instructions and can receive a new instruction every 1/1000th of a second.
• SRAM static random access memory
• Each micromirror is a light switch that can reflect light in one of two directions depending upon the state of the underlying memory cell. With the memory cell in the (1) state, the respective mirror rotates to a + 10°. With the memory cell in the (0) state, the respective mirror rotates to a -10°. Each mirror is capable of oscillating between these positions at rates of 1,000 cycles per second to produce pulses or bursts of reflected light.
• the digital light processing system is utilized in television and similar technologies to convert digital video signals into a visible digital display by transmitting to the human eye rapid digital light pulses that the eye interprets as a color analog image.
• the digital micromirror device which is available from Texas Instruments Incorporated, Dallas, Texas, is a high speed reflective digital light switch which when combined with image processing, memory, light source and optics forms a digital system capable of projecting large high contrast color images with excellent fidelity and consistency.
• the technology of digital light processing has not been related to the science of detecting and identifying biological molecules and pathogens.
• the object of the present invention is to unite the scientific technologies above described; specifically, to utilize the digital micromirror technology of Texas Instruments for the detection and identification of biologic molecules and pathogens.
• an array of microelectromechanical micromirrors is employed to detect, either by optical projection or through software interrogation, the presence of a molecule or biologic pathogen bonded on the surface of a micromirror that has been activated with an appropriate molecular probe.
• the multiplicity of mirrors in the array serve as test sites in a manner similar to the practice of the art as above described.
• Such use of an array of micromirrors as test sites provides a straight forward method to screen large numbers of target molecules or pathogens quickly and efficiently for bioactivity, identification, and subsequent testing.
• Molecular probes can be attached to the digital mirror surfaces by physical or chemical mechanisms.
• a physical method comprises adsorption or absorption of the probes onto the surfaces.
• a chemical method comprises bonding the probes onto the mirror surfaces by either ionic or covalent bonding.
• a practitioner would attach different bioluminescent or chemiluminescent probes to different mirror surfaces of the array, expose the array to a sample substance containing target molecules of interest, direct an appropriate light source onto the array, and project the resulting image on a screen or other surface. Locations where target molecules react with a probe will fluoresce in the projected image and the individual test sites (micromirrors) can be addressed with software to identify the precise location and the precise probe at that location for the molecule of interest.
• a software interrogation method for identifying target molecules utilizes the surface mass change on micromirrors oscillating at 1,000 cycles per second to detect the presence of molecular reactions at specific locations.
• molecular probes can be attached to the micromirrors, the array of mirrors can then be oscillated and exposed to a sample substance containing target molecules of interest, and if there is a chemical reaction at one or more probes, the mass of the respective mirrors will change and that will cause the rate of oscillation to change, i.e., slow down.
• the software will detect and identify the mirror or mirrors with slower oscillation and, knowing what probe was at that location, a target candidate can be identified.
• the identified mirror location can be covered with a photomask to protect the target molecule while the rest of the mirror array is washed with an appropriate solvent.
• the mask can then be removed by standard photolithography techniques, the target molecule washed off the mirror, identified and tested appropriately.
• the invention lends itself to high volume, fast, lost cost screening and identification of biologically active molecules and pathogens.

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• Health & Medical Sciences (AREA)
• Immunology (AREA)
• Life Sciences & Earth Sciences (AREA)
• Engineering & Computer Science (AREA)
• Molecular Biology (AREA)
• Biomedical Technology (AREA)
• Chemical & Material Sciences (AREA)
• Hematology (AREA)
• Urology & Nephrology (AREA)
• Biotechnology (AREA)
• Biochemistry (AREA)
• Cell Biology (AREA)
• Food Science & Technology (AREA)
• Medicinal Chemistry (AREA)
• Physics & Mathematics (AREA)
• Analytical Chemistry (AREA)
• Microbiology (AREA)
• General Health & Medical Sciences (AREA)
• General Physics & Mathematics (AREA)
• Pathology (AREA)
• Investigating Or Analysing Materials By The Use Of Chemical Reactions (AREA)
• Apparatus Associated With Microorganisms And Enzymes (AREA)
• Investigating, Analyzing Materials By Fluorescence Or Luminescence (AREA)

Applications Claiming Priority (2)

Publications (2)

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• 1997
  • 1997-12-23 US US08/996,845 patent/US5912181A/en not_active Expired - Fee Related
• 1998
  • 1998-12-23 DE DE69818957T patent/DE69818957T2/de not_active Expired - Fee Related
  • 1998-12-23 EP EP98124574A patent/EP0926495B1/de not_active Expired - Lifetime

Patent Citations (2)

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